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Aging of preleukemi...
Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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American Association for Cancer Research,2020
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-176999
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-176999URI
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https://doi.org/10.1158/2643-3230.BCD-20-0059DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Thénoz, Morgan
(author)
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Szarzyńska, Bronisława
(author)
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Landfors, Mattias,1977-Umeå universitet,Patologi(Swepub:umu)maslas98
(author)
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De Coninck, Stien
(author)
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Demoen, Lisa
(author)
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Provez, Lien
(author)
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Kuchmiy, Anna
(author)
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Strubbe, Steven
(author)
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Reunes, Lindy
(author)
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Pieters, Tim
(author)
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Matthijssens, Filip
(author)
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Van Loocke, Wouter
(author)
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Erarslan-Uysal, Büşra
(author)
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Richter-Pechańska, Paulina
(author)
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Declerck, Ken
(author)
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Lammens, Tim
(author)
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De Moerloose, Barbara
(author)
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Deforce, Dieter
(author)
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Van Nieuwerburgh, Filip
(author)
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Cheung, Laurence C.
(author)
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Kotecha, Rishi S.
(author)
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Mansour, Marc R.
(author)
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Ghesquière, Bart
(author)
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Van Camp, Guy
(author)
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Berghe, Wim Vanden
(author)
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Kowalczyk, Jerzy R.
(author)
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Szczepański, Tomasz
(author)
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Davé, Utpal P.
(author)
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Kulozik, Andreas E.
(author)
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Goossens, Steven
(author)
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Curtis, David J.
(author)
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Taghon, Tom
(author)
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Dawidowska, Małgorzata
(author)
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Degerman, Sofie,1977-Umeå universitet,Institutionen för klinisk mikrobiologi,Patologi,Sofie Degerman(Swepub:umu)soiden99
(author)
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Van Vlierberghe, Pieter
(author)
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Umeå universitetPatologi
(creator_code:org_t)
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In:Blood cancer discovery: American Association for Cancer Research1:3, s. 274-2892643-3249
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Roels, Juliette
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Thénoz, Morgan
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Szarzyńska, Bron ...
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Landfors, Mattia ...
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De Coninck, Stie ...
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Demoen, Lisa
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Provez, Lien
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Kuchmiy, Anna
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Strubbe, Steven
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Reunes, Lindy
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Pieters, Tim
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Matthijssens, Fi ...
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Van Loocke, Wout ...
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Erarslan-Uysal, ...
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Richter-Pechańsk ...
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Declerck, Ken
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Lammens, Tim
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De Moerloose, Ba ...
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Deforce, Dieter
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Van Nieuwerburgh ...
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Cheung, Laurence ...
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Kotecha, Rishi S ...
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Mansour, Marc R.
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Ghesquière, Bart
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Van Camp, Guy
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Berghe, Wim Vand ...
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Kowalczyk, Jerzy ...
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Szczepański, Tom ...
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Davé, Utpal P.
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Kulozik, Andreas ...
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Goossens, Steven
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Curtis, David J.
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Taghon, Tom
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Dawidowska, Małg ...
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Degerman, Sofie, ...
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Van Vlierberghe, ...
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